Epigenetic targeted therapy in DIPG

This project focuses directly on discovering potential cures for Diffuse Intrinsic Pontine Glioma (DIPG), the most aggressive of all childhood cancers.

Despite its poor prognosis, difficulty accessing biological samples has meant that little research has been performed into DIPG in the past. The Ziegler lab was the first in Australia to establish and run a dedicated DIPG research program with an extensive bank of tissue, cell cultures and in vivo models that provide a unique facility to investigate innovative therapies.

Research funded by The Kids’ Cancer Project has investigated the role of TRX-E-009-1, a novel anti-cancer agent and found that it effectively reduces DIPG cell viability in multiple DIPG patient samples. Moreover, TRX-E-009-1 can affect the epigenome when combined with histone deacetylase (HDAC) inhibition and is a promising combinatorial approach to treating DIPG.

This project builds on these findings to develop a new epigenetic modifying therapy in unique DIPG mouse models. Importantly, the novel epigenetic targeted drug CBL0137 will begin Phase 1 paediatric clinical trial testing in 2019/20 in an international COG trial led by Associate Professor Ziegler, with an expansion cohort for DIPG patients. He will identify the optimal epigenetic targeted combination therapy that will help define the further clinical development and Phase 2 expansion strategy of this exciting novel therapy.

The results of this project will lead directly to a rationally designed combination clinical trial that has the potential to directly impact on DIPG patients and improve their outcomes.